GAIT DISORDERS ARE a distinctive feature of idiopathic

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1 ORIGINAL ARTICLE Freezing of Gait and Activity Limitations in People With Parkinson s Disease Dawn M. Tan, M Physio, Jennifer L. McGinley, PhD, Mary E. Danoudis, M Physio, Robert Iansek, MD, PhD, Meg E. Morris, PhD ABSTRACT. Tan DM, McGinley JL, Danoudis ME, Iansek R, Morris ME. Freezing of gait and activity limitations in people with Parkinson s disease. Arch Phys Med Rehabil 2011;92: Objectives: To investigate the relationships between freezing of gait (FOG) and activity limitations in ambulant people with Parkinson s disease (PD), and to explore the contribution of FOG and gait hypokinesia to activity limitations after adjusting for the effects of disease severity. Design: Retrospective, cross-sectional design. Setting: Participants were recruited from neurologists clinics and the general public in metropolitan Melbourne, Australia. Participants: Volunteers were screened for eligibility using the following inclusion criteria: diagnosis of idiopathic PD, modified Hoehn and Yahr stages 0 to IV, without dementia. Participants (N 210) were tested (mean age SD, y; mean PD duration SD, y; median Hoehn and Yahr stage 2.5). Interventions: Not applicable. Main Outcome Measures: FOG was measured using the FOG questionnaire. Gait hypokinesia was quantified using both the 6-meter walk test and the Timed Up and Go test. Activity limitation was measured using the modified Unified Parkinson s Disease Rating Scale activities of daily living (ADL) section and the Schwab and England ADL scale. Results: Severity of gait freezing correlated significantly with the level of activity limitation (Spearman correlation coefficient,.49 to.48; P.001). A hierarchic regression model showed that disease severity explained 37.5% of the variance in Schwab and England ADL score (P.001). Gait hypokinesia and FOG severity scores explained an additional 9.1% of the variance in activity limitation (R 2 change.091; P.001). Conclusions: FOG severity and gait hypokinesia were associated with reduced levels of activity after adjusting for disease severity. Key Words: Gait disorders; Parkinson disease; Rehabilitation by the American Congress of Rehabilitation Medicine From the School of Health Sciences, University of Melbourne, Melbourne (Tan, McGinley, Danoudis, Morris); Murdoch Children s Research Institute, The Royal Children s Hospital, Melbourne (McGinley); Clinical Research Centre for Movement Disorders and Gait: Victorian Comprehensive Parkinson s Program, Kingston Centre, Melbourne (Danoudis, Iansek), Australia; and Department of Physiotherapy, Singapore General Hospital, Singapore (Tan). Presented in part as a poster at the World Parkinson Congress, September 28 October 1, 2010, Glasgow, UK. Supported by a Michael J. Fox Clinical Discovery Grant. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Reprint requests to Dawn M. Tan, M Physio (Neuro), Department of Physiotherapy, Singapore General Hospital, Outram Rd, Singapore , dawn.tan.m.l@sgh.com.sg /11/ $36.00/0 doi: /j.apmr GAIT DISORDERS ARE a distinctive feature of idiopathic Parkinson s disease (PD). Freezing of gait (FOG) is a particularly disabling sequela in many people with advanced disease. 1,2 FOG can be distressing 3 and incapacitating 1 for people with PD. Effective management of FOG can be a challenge 4 for clinicians given its episodic nature and limited responsiveness to parkinsonian medication. 5 There is limited evidence of the impact of FOG on function and disability in people with PD. This study explores the relationship between FOG and activity limitations in ambulant adults with PD. FOG is characterized by an inability to generate or sustain an effective stepping sequence, 6 leading to sudden blocks in walking. 7 It is frequently experienced during functional activities such as turning or step initiation. It can also be triggered by emotional stress, 8 environmental constraints, 9 dual tasking, 1 and directional change. 4 FOG has been associated with increased risk of falls 1,10,11 and can compromise quality of life. 12 In addition, people with PD may limit their community ambulation to minimize the occurrence of freezing episodes. 6 This may lead to reduced activity levels and exercise capacity. FOG occurs more commonly with increased PD duration, increased disease severity, and long duration of levodopa treatment. 6,13 There are relatively few studies of the relationships among FOG, gait speed, and activity limitations The extent to which the results of previous studies can be generalized to the population of people with PD is limited by small sample sizes, 14,16 nonrepresentative populations from drug trials, and a focus on patients with advanced disease. 2 Little is known about FOG in early PD. This study describes the frequency and characteristics of FOG in an Australian sample of ambulant adults with PD. It also explores relationships between FOG severity and subtypes (start and turn hesitations) and activity limitations. The relationships between FOG severity and gait hypokinesia are also investigated given the inconsistent reports of the associations between hypokinesia and FOG. 17,18 It was hypothesized that the frequency and severity of FOG subtypes would vary according to disease stage. It was also predicted that relationships would exist between FOG severity and the severity of gait hypokinesia and between FOG severity and activity limitations. METHODS The study used baseline data from an existing trial that investigated the effect of exercise on mobility and falls. 19 A ADL FOG FOG-Q MMSE PD TUG UPDRS List of Abbreviations activities of daily living freezing of gait Freezing of Gait Questionnaire Mini-Mental State Examination Parkinson s disease Timed Up & Go Unified Parkinson s Disease Rating Scale 1159

2 1160 FREEZING OF GAIT IN PARKINSON S DISEASE, Tan total of 210 people diagnosed with PD who lived in metropolitan Melbourne were recruited according to the following inclusion criteria: idiopathic Parkinson s disease, modified Hoehn and Yahr 20 stages 0 to 4, ability to provide informed consent (determined by age and educational level-adjusted Mini-Mental State Examination (MMSE) normative scores 21,22 ), no dementia, health status permitting safe participation in a strength training exercise program, and ability to attend an outpatient 8-week therapy program. We also recorded each person s age, sex, disease duration, and Hoehn and Yahr stage. Ethical approval was gained from the University of Melbourne Health Sciences Human Ethics Sub-Committee (no ), and all participants provided written informed consent. Assessments were conducted by physiotherapists trained in administration of the measurement protocol. Outcome measures. Data for 210 participants were analyzed. The primary outcome measures included measures of hypokinesia (TUG 23 and gait speed calculated from 6-m walk test 24,25 scores) and FOG (Freezing of Gait Questionnaire [FOG-Q]). 14,15 The FOG-Q is a validated and reliable selfreported questionnaire It is composed of 6 items (item score ranges 0 4) that are summed to yield a total score (ranging 0 24). Higher total scores indicate more severe FOG. A FOG-Q modified total score that quantifies FOG severity was obtained by adding the score of questions 3, 4, 5, and 6 because these are questions specific to FOG. Questions 1 and 2 were not included because they are general questions relating to gait. Activity limitations were assessed with the Unified Parkinson s Disease Rating Scale (UPDRS) Section II ADL 26,27 (higher score indicates greater activity limitation) and Schwab and England activities of daily living (ADL) scale (higher score indicates lower level of activity limitation). 28 The original UPDRS ADL scores were modified by excluding gait-related scores (UPDRS items 14 on FOG and 15 on gait) similar in construct to the independent variables (FOG and gait hypokinesia) so that the assumptions of independence for correlation and regression analyses were not violated. 29 The Schwab and England gives a percentage of the ability to perform ADL, whereas the UPDRS ADL assesses the ability to perform a range of specific ADL tasks and motor function (speech, salivation). Hence, both instruments were used as measures of disability. Disease severity was measured using the UPDRS Section III motor score. 30,31 Statistical Analysis Data were analyzed using SPSS statistical software (Version 18.0). a Demographic data, FOG occurrence, and FOG characteristics were initially analyzed using descriptive statistics. Participants were identified as having FOG if they obtained a score of more than 0 for the FOG-Q items 3, 15 4, 5, or 6 because these questions are specific to FOG. Because FOG-Q items 1 and 2 are related to general walking difficulties, they were not included in analyses of FOG. Participants were categorized into (1) very early disease, Hoehn and Yahr stages 0 to 1.5; (2) early disease, stages 2 to 2.5; (3) moderate disease, stage 3; and (4) advanced disease, stage The association between disease state and FOG was analyzed using the chisquare test. The McNemar test was used to investigate differences between the incidence of start and turn hesitations among participants who experienced FOG. The Kruskal-Wallis test was used to explore the differences in FOG severity (FOG-Q modified total score), FOG frequency (FOG-Q item 3), FOG duration (FOG-Q item 4), severity of start hesitation FOG (FOG-Q item 5), and severity of turning hesitation FOG (FOG-Q item 6) in participants with different disease states. We performed post hoc tests using Bonferroni Table 1: Clinical Characteristics of Participants Clinical Characteristic (Measure) Mean SD Range n Age (y) Disease duration (y) Cognition (MMSE score) Disease severity (UPDRS total) FOG severity (FOG-Q total score) Activity limitation UPDRS ADL section Schwab and England ADL scale Stage of disease (HY) Very early (HY stage 0 1.5) 34 Early (HY stage 2 2.5) 89 Moderate disease (HY stage 3) 63 Advanced disease (HY stage 4) 24 Abbreviation: HY, Hoehn and Yahr. corrections to the alpha levels to control for type 1 errors to investigate further the differences among the 4 groups. The Kruskal-Wallis test was also used to investigate whether turn hesitation severity was greater than start hesitation severity in patients with different disease states. The nonparametric version of the 1-way analysis of variance test was necessary because the assumption of homogeneity of variance was violated. Spearman correlation coefficients were used to analyze the relationships between participant demographics and activity limitations, FOG severity (modified FOQ-Q total score) and activity limitations, and gait hypokinesia and activity limitations, because these variables were not normally distributed. Hierarchic multiple regression was used to assess the contribution of gait hypokinesia and FOG severity (modified FOG-Q total score) to levels of activity limitation after adjusting for the influence of disease severity. Preliminary analyses were conducted to ensure that the assumptions of normality, linearity, multicollinearity, and homoscedasticity were not violated. The alpha levels for all tests were set at.05 unless otherwise indicated. RESULTS Of the 210 participants, 140 (66.7%) were men and 70 (33.3%) were women. The clinical characteristics of the participants are detailed in table 1. One hundred ten (52%) of the participants experienced FOG. The subtypes, frequency, and duration of FOG are summarized in table 2 and figure 1. The occurrence of FOG was higher in people with more advanced disease states ( 2 [2,n 209] 36.7; P.001). The proportions of participants in the very early, early, moderate, and advanced disease states who experienced FOG were 27.3%, 38.2%, 76.2%, and 79.2%, respectively. Characteristics of FOG in Participants With Early, Moderate, and Advanced Disease FOG severity (modified FOG-Q total score) was found to differ across the 4 PD disease-stage groups ( 2 [3,n 209] 39.24; P.001). The group with moderate disease recorded the highest median FOG total score of 6 compared

3 FREEZING OF GAIT IN PARKINSON S DISEASE, Tan 1161 Table 2: Subtypes, Frequency, and Duration of FOG in Participants Who Experienced FOG Characteristics of FOG (Measure Used) No. of Participants (%) Subtype Start hesitation FOG (FOG-Q item 5) 95 (86.4) Took longer than 1s to start walking 42 (44.2) Took longer than 3s to start walking 32 (33.7) Took longer than 10s to start walking 14 (14.7) Took longer than 30s to start walking 7 (7.4) Turn hesitation FOG (FOG-Q item 6) 78 (70.9) Able to resume turning in 1 2s 43 (55.1) Able to resume turning in 3 10s 24 (30.7) Unable to resume turning for 11 30s 8 (10.3) Unable to resume turning for more 3 (3.8) than 30s Frequency of any FOG (FOG-Q item 3) Very rarely about once a month 29 (27.1) Rarely about once a week 26 (24.2) Often about once a day 39 (36.4) Always whenever walking 13 (12.1) Duration of worst FOG (FOG-Q item 4) 1 2s 52 (47.3) 3 10s 31 (28.2) 11 30s 8 (7.3) Unable to walk for more than 30s 11 (10) with the advanced, early, and very early disease groups (medians of 5.5, 0, and 0, respectively). Post hoc analyses showed that the main differences were found between the groups with very early disease and the moderate and advanced disease groups. Similarly, FOG severity in the early disease group was also significantly different from the groups with moderate and advanced disease states. FOG was less severe in the groups with very early and early disease compared with both the moderate and advanced disease groups (P.001). The early and very early disease groups did not significantly differ in FOG severity. Likewise, FOG severity did not differ between the moderate and advanced disease groups. Similar results were also found for FOG frequency, duration, and start and turn hesitation severity with increased severity of symptoms in moderate and advanced disease. Figure 1 shows the distribution of FOG characteristics across the 4 disease severity groups. The box represents the distribution of FOG scores in each disease category. The length of the box represents the interquartile range and the protruding lines (whiskers) from the box go to the smallest and largest value of the distribution. The line across the inside of the box represents the median value. The circles represent outliers (extending 1.5 length from the edge of the box) while asterisks represent extreme scores (extending more than 3 box lengths from the edge of the box). Differences in Start and Turn Hesitation FOG Subtypes and Severity in Participants With Very Early, Early, Moderate, and Advanced Disease Start hesitation (86.4%) was more frequent than turn hesitation (70.9%) among participants who experienced FOG (P.05). However, the differences between turn and start hesitation severity were not significant across the 4 disease severity groups ( 2 [3,n 209] 4.53; P.21). Relationships Between FOG and Level of Activity Limitation The relationships between FOG and levels of activity limitation are summarized in table 3. There was a moderately strong positive relationship between FOG severity and activity limitation measured by the modified UPDRS ADL score (.48; P.001; n 208). Similarly, there was a moderately strong negative relationship between FOG severity (FOG-Q modified total score) and activity limitation measured by Schwab and England ADL scale (.49; P.001; n 208). In addition, FOG characteristics (frequency and duration) and subtypes (start and turning hesitation) also correlated with activity limitations with highly similar strengths of associations. Table 3 reports the associations between selected patient demographic characteristic and disability, gait hypokinesia and disability, and disease severity and disability. Only gait hypokinesia (measured by gait speed and Timed Up & Go (TUG)) and disease severity (measured by UPDRS motor scores) showed moderate and strong associations with disability (P.001). Contribution of FOG and Gait Hypokinesia to Activity Limitation in People With PD Variables that demonstrated moderate and significant associations with activity limitations were used in the hierarchic regression. Using the modified UPDRS ADL score as the dependent variable, UPDRS motor score entered at step 1 explained 41.2% of the variance in the modified UPDRS ADL scores. After entry of gait speed, TUG, and FOG severity scores at step 2, the total variance explained by the model as a whole was 47.8% (F 3, ; P.001). FOG severity and gait hypokinesia explained an additional 6.7% of the variance in activity limitations after adjusting for disease severity (R 2 change.067; F change 3, ; P.001). In the final model (table 4), only disease and FOG severity and hypokinesia in turning were significantly associated with activity limitations, with disease severity recording the highest beta value (.50; P.001), followed by FOG severity (.29; P.001) and hypokinesia in turning (.14; P.048). The regression modeling was repeated using activity limitation (measured by Schwab and England ADL scale) as the dependent variable. Disease severity initially explained 37.5% of the variance in activity limitation. After entry of gait speed, TUG, and FOG severity at step 2, the total variance explained by the model as a whole was 46.6% (F 4, ; P.001). FOG severity and gait hypokinesia measured by gait speed and TUG explained an additional 9.1% of the variance in activity limitation after adjusting for disease severity (R 2 change.091; F change 3, ; P.001). In the final model, only 2 predictors remained significantly associated with activity limitations, with disease severity recording the highest beta value (.42; P.001), followed by FOG severity ( 0.34; P.01). Relationships Between FOG Severity and Gait Hypokinesia There was a moderately strong positive relationship between FOG severity (FOG-Q modified total score) and gait hypokinesia measured by the TUG test (.30; P.001; n 195). There was a slightly weaker negative relationship between FOG severity (FOG-Q modified total score) and gait hypokinesia measured by gait speed (.23; P.001; n 195).

4 1162 FREEZING OF GAIT IN PARKINSON S DISEASE, Tan Fig 1. FOG severity and characteristics in very early, early, moderate, and advanced disease.

5 FREEZING OF GAIT IN PARKINSON S DISEASE, Tan 1163 Table 3: Relationships Between FOG and Activity Limitations Variable (Measurement) Levels of Activity Limitations Modified UPDRS ADL Score Schwab and England ADL Scale FOG characteristics (n 208) FOG severity (FOG-Q modified total score) FOG frequency (FOG-Q item 3) Duration of worst FOG (FOG-Q item 4) Start hesitation severity (FOG-Q item 5) Turn hesitation severity (FOG-Q item 6) Gait hypokinesia (n 195) Gait speed (m/s) TUG Participant characteristics (n 209) Age.05*.17 Disease duration Disease severity (UPDRS motor score) NOTE. Values indicate Spearman correlation coefficients. *P.05 (2-tailed); P.001 (2-tailed). DISCUSSION More than half of the participants in this sample of ambulant people with PD experienced FOG. This was similar to previous studies 2,32 that reported occurrences of FOG in 53% to 55% of study samples. In contrast, Giladi et al 15 reported an incidence of FOG in 86% of his sample recruited from medical centers in Europe, Israel, and Argentina. This may have been related to the advanced disease status of these participants who were also participating in a drug trial. Similar to previous studies, 13,33 the current study demonstrated that start hesitations (87%) appeared to be more frequent than turn hesitations (71%). Nevertheless, there were no differences in start and turn hesitation severity in participants at each disease stage. In contrast with the current findings, Schaafsma et al 34 reported that turn hesitations were more frequent than start hesitations during both on and off states in a smaller sample of 19 patients with freezing episodes. FOG was measured via a self-reported questionnaire in the current study, while FOG in the study by Schaafsma 34 was observed under laboratory settings in which participants had to walk through a planned course and freezing episodes were videotaped. Moore et al 35 also reported a higher number of freezing episodes encountered during turning compared with gait initiation in a group of 11 participants with PD using an ambulatory monitoring device in a controlled laboratory setting. The authors demonstrated that high-frequency components of leg movement (leg trembling) using an ankle mounted sensor occurred during FOG episodes in gait initiation, turning, and encountering obstacles. Akinesia (complete lack of movement) was not observed. The differences in the frequency of start and turn hesitation subtypes in our study compared with the findings of Schaafsma 34 and Moore 35 may be a result of the different methods of measuring FOG. FOG severity, frequency, and start and turn hesitation severity were associated with increased levels of activity limitation. This was in agreement with Nilsson and Hagell 16 and Giladi et al. 14,15 FOG severity was also associated with reduced walking speed. These results were supported by previous studies that demonstrated gait-related problems were important factors in disease progression and quality of life. 36,37 FOG severity contributed to levels of activity limitations after adjusting for disease severity and was a stronger predictor of activity limitation than gait hypokinesia. This finding has important clinical implications. First, consideration could be given to assessing FOG in all patients, even those with early disease, as it occurs across the PD lifespan. Second, timed measures like the TUG and 6-meter walk test only correlated Table 4: Relationships Between Activity Limitations, Disease Severity, FOG, and Gait Hypokinesia Using Hierarchical Regression Analysis Predictors A. Model Using the Modified UPDRS ADL Scores as the Dependent Variable Unstandardized Coefficients B Standardized Coefficients Lower Bound 95% CI for B Upper Bound 1 UPDRS motor UPDRS motor Gait speed TUG score.09.14* FOG severity *P.05; P.001. B. Model Using the Schwab and England ADL Scale as the Dependent Variable Unstandardized Coefficients B Standardized Coefficients 95% CI for B Lower Bound Unstandardized Coefficients B Upper Bound 1 UPDRS motor * UPDRS motor * Gait speed TUG score FOG severity * Abbreviation: CI, confidence interval. *P.001.

6 1164 FREEZING OF GAIT IN PARKINSON S DISEASE, Tan with FOG severity with low to moderate strength. FOGspecific tools like the FOG-Q may be useful additions to screen FOG. It may also be useful to assess objectively patients walking in a range of environmental conditions that typically induce FOG, such as walking through doorways, narrow passages, and crowded rooms. Early detection of FOG might inform the selection of interventions such as the use of external cues 38 or attentional strategies to minimize its impact on activity limitations. Study Limitations One potential limitation of the study includes the accuracy of the FOG-Q in identifying freezing, given that it is a self-report questionnaire. Participants may not be able to differentiate between a freezing episode and off-phase akinesia leading to the false reporting of FOG. There is also a possibility that FOG may be underreported using this method of assessment as patients become desensitized to the consequences of FOG. 39 The new FOG questionnaire developed by Nieuwboer et al 39 may provide a more accurate option. In addition to a questionnaire component, it consists of a video portraying the different types and durations of FOG during walking through a doorway, turning, and gait initiation with a timer showing real-time estimates of FOG episodes. 39 The authors reported that the video had a small impact on the accuracy of detecting FOG episodes, but it helped influence the scoring of FOG severity of people with PD. The greatest difficulty in accurately detecting FOG episodes is the lack of a criterion standard measurement against which other tools are validated. Activity monitoring that has been tested in a controlled, laboratory-based environment may provide a promising option of detecting FOG in the homes of patients in the future. 35 Until the development of more validated tools, the current FOG-Q provides a useful estimate of FOG severity in patients with PD. Another limitation of this study involves the clinical profile of participants. The sample recruited was made up predominantly of participants with early to moderate disease, and the sample may not be representative of those who are severely affected. CONCLUSIONS FOG occurs throughout the time course of idiopathic PD and is associated with increased levels of activity limitation even after adjusting for disease severity. It is recommended that clinicians consider screening FOG in patients at all stages of the disease using FOG-specific tools tailored to the needs of people with PD. References 1. Bloem BR, Hausdorff JM, Visser JE, Giladi N. Falls and freezing of gait in Parkinson s disease: a review of two interconnected, episodic phenomena. Mov Disord 2004;19: Giladi N, Treves TA, Simon ES, et al. Freezing of gait in patients with advanced Parkinson s disease. J Neural Transm 2001;108: Backer JH. The symptom experience of patients with Parkinson s disease. J Neurosci Nurs 2006;38: Snijders AH, Nijkrake MJ, Bakker M, Munneke M, Wind C, Bloem BR. Clinimetrics of freezing of gait. Mov Disord 2008; 23(Suppl 2): Giladi N, McDermott MP, Fahn SM, et al. Freezing of gait in PD: prospective assessment in the DATATOP cohort. Neurology 2001;56: Morris ME, Iansek R, Galna B. Gait festination and freezing in Parkinson s disease: pathogenesis and rehabilitation. Mov Disord 2008;23(Suppl 2): Giladi N, Nieuwboer A. Understanding and treating freezing of gait in parkinsonism, proposed working definition, and setting the stage. Mov Disord 2008;23(Suppl 2): Giladi N, Hausdorff JM. The role of mental function in the pathogenesis of freezing of gait in Parkinson s disease. J Neurol Sci 2006;248: Giladi N, Kao R, Fahn S. Freezing phenomenon in patients with parkinsonian syndromes. Mov Disord 1997;12: Gray P, Hildebrand K. Fall risk factors in Parkinson s disease. J Neurosci Nurs 2000;32: Grimbergen YA, Munneke M, Bloem BR. Falls in Parkinson s disease. Curr Opin Neurol 2004;17: Moore O, Kreitler S, Ehrenfeld M, Giladi N. Quality of life and gender identity in Parkinson s disease. J Neural Transm 2005;112: Lamberti P, Armenise S, Castaldo V, et al. Freezing gait in Parkinson s disease. Eur Neurol 1997;38: Giladi N, Shabtai H, Simon ES, Biran S, Tal J, Korczyn AD. Construction of freezing of gait questionnaire for patients with Parkinsonism. Parkinsonism Relat Disord 2000;6: Giladi N, Tal J, Azulay T, et al. Validation of the Freezing of Gait Questionnaire in patients with Parkinson s disease. Mov Disord 2009;24: Nilsson MH, Hagell P. Freezing of Gait Questionnaire: validity and reliability of the Swedish version. Acta Neurol Scand 2009; 120: Iansek R, Huxham F, McGinley J. The sequence effect and gait festination in Parkinson disease: contributors to freezing of gait? Mov Disord 2006;21: Bartels AL, Balash Y, Gurevich T, Schaafsma JD, Hausdorff JM, Giladi N. Relationship between freezing of gait (FOG) and other features of Parkinson s: FOG is not correlated with bradykinesia. J Clin Neurosci 2003;10: Watts JJ, McGinley JL, Huxham F, et al. Cost effectiveness of preventing falls and improving mobility in people with Parkinson disease: protocol for an economic evaluation alongside a clinical trial. BMC Geriatr 2008;8: Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology 1967;17: Crum RM, James CA, Bassett SS, Folstein MF. Population-based norms for the Mini-Mental State Examination by age and educational level. JAMA 1993;269: Folstein MF, Folstein SE, Fanjiang G. MMSE Minimental State Examination clinical guide. Tampa: Psychological Assessment Resources, Inc; Morris S, Morris M, Iansek R. Reliability of measurements obtained with the Timed Up and Go test in people with Parkinson s disease. Phys Ther 2001;81: Morris M, Iansek R, Matyas T, Summers J. The pathogenesis of gait hypokinesia in Parkinson s disease. Brain 1994;117: Schenkman M, Cutson T, Kuchibhatla M, Chandler J, Pieper C. Reliability of impairment and physical performance measures for persons with Parkinson s disease. Phys Ther 1997;77: Goetz CG. The Unified Parkinson s Disease Rating Scale (UPDRS): status and recommendations. Mov Disord 2003;18: Marchese R, Bove M, Abbruzzese G. Effect of cognitive and motor tasks on postural stability in Parkinson s disease: a posturographic study. Mov Disord 2003;18: Schwab RS, England JA. Projection technique for evaluating surgery in Parkinson s disease. In: Gillingham FJ, Donaldson IM, editors. Third symposium on Parkinson s disease. Edinburgh: E & S Livingstone; p Portney LG, Watkins MP. Foundations of clinical research: applications to practice. 2nd ed. Hackensack: Prentice Hall Health; Alves G, Wentzel-Larsen T, Aarsland D, Larsen JP. Progression of motor impairment and disability in Parkinson disease: a population-based study. Neurology 2005;65:

7 FREEZING OF GAIT IN PARKINSON S DISEASE, Tan Zhao YJ, Wee HL, Chan YH, et al. Progression of Parkinson s disease as evaluated by Hoehn and Yahr stage transition times. Mov Disord 2010;25: Moore O, Peretz C, Giladi N. Freezing of gait affects quality of life of peoples with Parkinson s disease beyond its relationships with mobility and gait. Mov Disord 2007;22: Giladi N, McMahon D, Przedborski S, et al. Motor blocks in Parkinson s disease. Neurology 1992;42: Schaafsma JD, Balash Y, Gurevich T, Bartels AL, Hausdorff JM, Giladi N. Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson s disease. Eur J Neurol 2003;10: Moore ST, MacDougall HG, Ondo WG. Ambulatory monitoring of freezing of gait in Parkinson s disease. J Neurosci Methods 2008;167: Schrag A. Quality of life and depression in Parkinson s disease. J Neurol Sci 2006;248: Shulman LM, Gruber-Baldini AL, Anderson KE, et al. The evolution of disability in Parkinson disease. Mov Disord 2008;23: Lim I, van Wegen E, de Goede C, et al. Effects of external rhythmical cueing on gait in patients with Parkinson s disease: a systematic review. Clin Rehabil 2005;19: Nieuwboer A, Rochester L, Herman T, et al. Reliability of the new freezing of gait questionnaire: agreement between patients with Parkinson s disease and their carers. Gait Posture 2009; 30: Supplier a. SPSS, Level 9, IBM Centre, 601 Pacific Highway, St Leonards NSW 2065, Australia.

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